Exposure of human ovarian carcinoma to cisplatin transiently sensitizes the tumor cells for liposome-mediated gene transfer.

Human ovarian carcinoma cells (line 2008) grown as subcutaneous solid tumor in the severe combined immunodeficient mouse can be transfected by directly injecting a plasmid DNA-liposome complex into the tumor (in situ lipofection). The level of reporter gene expression in the tumor cells was significantly elevated if the animal received a single i.p. injection of cisplatin 1 week before the lipofection. Sensitization of the tumor for lipofection peaked 1 week after cisplatin injection and declined thereafter. Cells exposed to low concentration of cisplatin in vitro for four to five doubling times also showed elevated sensitivity for lipofection in vitro. Cisplatin was the only anticancer drug tested that exhibited this activity. These results suggest a sequential combinational gene therapy protocol with cisplatin for the ovarian carcinoma.